Repeat Infusions of CD19 CAR-T Cells: Factors Associated with Response, CAR-T Cell In Vivo Expansion, and Progression-Free Survival
Year: 2020
Type: article
Abstract: Background CD19-targeted chimeric antigen receptor-engineered (CD19 CAR)-T cell immunotherapy has shown efficacy for relapsed or refractory (R/R) B-cell malignancies, but absence of complete response or relapses are still observed in a significant portion of patients (pts). Objectives To evaluate outcomes after repeat infusion of CD19 CAR-T cells, and identify the factors associated with response, CAR-T cell in vivo expansion, and progression-free survival (PFS). Methods We analyzed data from pts with R/R B-cell malignancies who received a second infusion of CD19 CAR-T cells (CART2) on a phase 1/2 trial (NCT01865617) at our institution. Responses were evaluated 4 weeks after CAR-T cell infusion and defined according to the 2018 NCCN guidelines for acute lymphoblastic leukemia (ALL), 2018 iwCLL for chronic lymphocytic leukemia (CLL), and the Lugano criteria for non-Hodgkin lymphoma (NHL). Results Forty-four pts evaluable for response were included in this study (see Table). Pts were heavily pre-treated (median prior therapies, 6), and 16 pts (36%) had bulky (e 5cm) disease. Prior to CART2, 15 pts (32%) had not responded to CART1, 22 (50%) relapsed or progressed after initial response (complete response [CR], n=15; partial response [PR], n=7) to CART1, and 7 (16%) were in ongoing PR. We observed responses to CART2 in 3 of 14 ALL pts (21%; all CR/CRi), 4 of 11 CLL pts (36%; CR/CRi, n=3; partial response [PR], n=1), and 9 of 19 NHL pts (47%; CR, n=2; PR, n=7). After a 43-month median follow-up, the estimated 4-year PFS and OS probabilities in responders were 23% (95% CI, 9-59%) and 36% (95% CI 19-71%), respectively. Multivariable logistic regression identified lymphodepletion intensity before CART1 (high-intensity cyclophosphamide and fludarabine [CyFlu] vs Other, OR=12.19, p=0.04; high intensity versus low intensity CyFlu, OR=3.83, p=0.08) and the peak blood CAR-T cell count after CART2 (OR=2.31 per log10 CD8+ CAR-T cell/µL increase, p=0.01) as predictors of response to CART2. In a multivariable Cox model, higher peak CD8+ CAR-T cell count after CART2 (HR=0.47 per log10 CD8+ CAR-T cell/µL increase, p Conclusion Outcomes after second infusions of CD19 CAR-T cells might be improved with high-intensity CyFlu lymphodepletion prior to CART1 and by increasing the CAR-T cell dose at the time of CART2.
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,650
OpenAlex ID: W3001737745